The microenvironment dictates glycocalyx construction and immune surveillance

Author:

Tharp Kevin M.,Park SangwooORCID,Timblin Greg A.ORCID,Richards Alicia L.,Berg Jordan A.,Twells Nicholas M.,Riley Nicholas M.ORCID,Peltan Egan L.,Shon D. Judy,Stevenson Erica,Tsui Kimberly,Palomba Francesco,Lefebvre Austin E. Y. T.,Soens Ross W.,Ayad Nadia M.E.,ten Hoeve-Scott Johanna,Healy Kevin,Digman Michelle,Dillin Andrew,Bertozzi Carolyn R.,Swaney Danielle L.,Mahal Lara K.,Cantor Jason R.,Paszek Matthew J.,Weaver Valerie M.

Abstract

SummaryEfforts to identify anti-cancer therapeutics and understand tumor-immune interactions are built within vitromodels that do not match the microenvironmental characteristics of human tissues. Usingin vitromodels which mimic the physical properties of healthy or cancerous tissues and a physiologically relevant culture medium, we demonstrate that the chemical and physical properties of the microenvironment regulate the composition and topology of the glycocalyx. Remarkably, we find that cancer and age-related changes in the physical properties of the microenvironment are sufficient to adjust immune surveillance via the topology of the glycocalyx, a previously unknown phenomenon observable only with a physiologically relevant culture medium.Key PointsCulture medium dictates cellular mechanoresponse signatures in vitroEpithelial glycocalyx construction is mediated by Heat Shock Factor 1 (HSF1)Sialic acid topology dictates Natural Killer cell cytotoxicityPhysiological microenvironments reveal distinct glycobiology

Publisher

Cold Spring Harbor Laboratory

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